The proposed research is to elucidate the chemistry and biosynthesis of algal and other aquatic toxins which have serious impact on public health. The chemical work is intended to provide basic information to design preventive and curative measures, and also to discover new site-specific toxins as tools to investigate important biological mechanisms involving neural receptors such as sodium channels and glutamate receptors. The biosynthesis work is intended to elucidate the sites of formation and unique metabolic pathways in aquatic organisms. The resulting information will help to consider such important issues as the virulency acquisition of red tide organisms and marine animals, and the mass production of important marine products. Specifically, the structures, distribution, and biosynthesis of 1) excitatory amino acids such as domoic acid and kainic acid; 2) paralytic shellfish poisons (PSP) such as saxitoxin and gonyautoxins; 3) polyether toxins such as brevetoxins and okadaic acid derivatives; 4) blue-green algal toxins such as cyanoginosins and aphanorphin; 5) tetrodotoxin and its derivatives will be investigated. The work will involve the culturing of organisms, analysis and purification of toxins using chromatographic methods, structure elucidation by modern spectroscopic methods such as 2D-NMR and X-ray crystallography, and isotope labeling studies using both stable and radioactive isotopes. Isolated toxins will be provided to neurophysiologists for pharmacological studies.